Low-dose aspirin intended for primary prevention, typically 75 to 100 mg once daily, does not protect against cardiovascular events in persons who weigh at least 70 kg, suggests a patient-level analysis of randomized trials that included more than 100,000 patients.

That low-dose aspirin seems protective only in lighter adults has major implications for the primary prevention strategy. About half of women and 80% of the men weighed at least 70 kg in the meta-analysis of mostly older trials of primary prevention aspirin. 

The study was published in the Lancet, with lead author Peter M. Rothwell, MD, University of Oxford John Radcliffe Hospital, United Kingdom. "We showed fairly convincingly that in the trials done 10 or 20 years ago, there was weight dependence, and those on the right dose per weight seemed to benefit quite a lot in primary prevention," Rothwell told.

"Best Estimate at the Moment"

Low-dose aspirin was associated with a 12% drop in risk for CV events (vascular death, myocardial infarction, or stroke) overall in the primary prevention population (P = .0008) but a decrease of 23% for people weighing less than 70 kg (P < .0001). The risk edged nonsignificantly lower in the remaining people 70 kg or heavier (P = .24).

"It is the best estimate that we have got at the moment: You would have to say that the low-dose aspirin does seem to work in people under 70 kg," Rothwell said.

He acknowledged, however, that the degree of CV protection seen in the analysis "might well be smaller now than it was 10 to 20 years ago" given the rise of statins and other treatment advances in the intervening years.

Although any of the conventional low aspirin doses appear protective in people who weigh less than 70 kg, "there is a question mark about the need for higher doses at higher weights," he said.

The CV risk reduction was about 17% for persons 70 kg or heavier at a daily aspirin dose of 325 mg (P = .028), which should be weighed against the possibility of bleeding and other attendant risks.

"Even with low-dose aspirin, the risk for bleeding complications was weight-dependent, dissipating with increasing weight to about 90 kg (about 198 pounds). That a bleeding risk was observed in people weighing 70 to 90 kg "is not good news," Rothwell said. "Then you are probably not getting much benefit at all, and possibly harm if you are talking the low dose."

Fodder for Future Trials

Because half the women and most of the men in the analysis weighed more than 70 kg, authors of an accompanying editorial point out, "weight-adjusted dosing would result in increased daily doses of aspirin in the majority of patients."

That would be expected to increase the risk for bleeding, but perhaps not in a linear fashion, write Katherine N. Theken, PharmD, and Tilo Grosser, MD, from the University of Pennsylvania, Philadelphia.

"Bodyweight should be considered in ongoing and future randomized clinical trials that address aspirin dosing in cardiovascular prevention to clarify how weight-adjusted dosing will affect both benefit and risk," they concluded.